Nucleophosmin3 carried by small extracellular vesicles contribute to white adipose tissue browning

Yan Zhang1,2,3, Mei Yu4,5,6, Jia Dong7,1,2,8

  • 1National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, China.

Abstract

Insights

Small extracellular vesicles from brown adipose tissue (sEVs-BAT) transfer Nucleophosmin3 (NPM3), a key factor promoting white adipose tissue (WAT) browning. Supplementing sEVs-BAT may offer a therapeutic strategy for obesity and metabolic diseases.

Area of Science:

  • Metabolic Regulation
  • Adipose Tissue Biology
  • Extracellular Vesicle Research

Background:

  • White adipose tissue (WAT) browning is a therapeutic target for obesity and metabolic diseases.
  • Small extracellular vesicles (sEVs) from adipose tissue (sEVs-AT) are emerging regulators of systemic metabolism.
  • The specific roles of sEVs-AT contents in WAT browning remain unclear.

Purpose of the Study:

  • To investigate the role of specific contents within sEVs-AT in regulating WAT browning.
  • To identify novel factors transferred by sEVs-BAT that influence adipose tissue metabolism.

Main Methods:

  • Investigated Nucleophosmin3 (NPM3) transfer via sEVs derived from brown adipose tissue (sEVs-BAT).
  • Assessed the impact of sEVs-BAT on browning-related gene expression in 3T3-L1 preadipocytes and WAT.
  • Examined the effects of NPM3 knockdown in brown adipose tissue (BAT) on sEVs-BAT-mediated WAT browning and weight loss in an obesity model.

Main Results:

  • Nucleophosmin3 (NPM3) was identified as a key cargo of sEVs-BAT, acting as a batokine.
  • NPM3 transfer by sEVs-BAT induced WAT browning by enhancing PRDM16 mRNA stability.
  • Knockdown of NPM3 in BAT abrogated the WAT browning and weight loss effects of sEVs-BAT in obesity.

Conclusions:

  • NPM3 plays a crucial role in regulating WAT browning through sEV-mediated transfer.
  • sEVs-BAT represents a promising therapeutic strategy for enhancing thermogenesis and energy expenditure.
  • This study provides new insights into the molecular mechanisms of WAT browning and potential obesity treatments.

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